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Cited by 295Immunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkersinterferon and immune responses

Chemotherapeutics and Radiation Stimulate MHC Class I Expression through Elevated Interferon-beta Signaling in Breast Cancer Cells

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Wan, Shan, Pestka, Sidney, Jubin, Ronald G., Lyu, Yi Lisa, Tsai, Yu-Chen, Liu, Leroy F.·2012·PLoS ONE
DOI 10.1371/journal.pone.0032542PMC PMC3291570
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Abstract

Low doses of anticancer drugs have been shown to enhance antitumor immune response and increase the efficacy of immunotherapy. The molecular basis for such effects remains elusive, although selective depletion of T regulatory cells has been demonstrated. In the current studies, we demonstrate that topotecan (TPT), a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I) expression in breast cancer cells through elevated expression/secretion of interferon-β (IFN-β) and activation of type I IFN signaling. First, we show that TPT treatment elevates the expression of both total and cell-surface MHC I in breast cancer cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells induce elevated expression of cell-surface MHC I in drug-naïve recipient cells, suggesting the involvement of cytokines and/or other secreted molecules. Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines such as IFN-β, TNF-α, IL-6 and IL-8. Third, either knocking down the type I interferon receptor subunit 1 (IFNAR1) or addition of neutralizing antibody against IFN-β results in reduced MHC I expression in TPT-treated cells. Together, these results suggest that TPT induces increased IFN-β autocrine/paracrine signaling through type I IFN receptor, resulting in the elevated MHC I expression in tumor cells. Studies have also demonstrated that other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and vinblastine) similarly induce increased IFN-β secretion and elevated MHC I expression. In addition, conditioned media from γ-irradiated donor cells are shown to induce IFN-β-dependent MHC I expression in unirradiated recipient cells. In the aggregate, our results suggest that many cancer therapeutics induce elevated tumor antigen presentation through MHC I, which could represent a common mechanism for enhanced antitumor immune response through T cell cytotoxicity during metronomic chemotherapy, as well as increased efficacy of combined chemo- (or radio-)/immuno-therapy.

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  • Cisplatin, etoposide, and paclitaxel can stimulate tumor cells to produce IFN-b, serving as a signaling molecule that orchestrates expression of MHC class I molecules critical for antigen presentation.

    “cisplatin, etoposide, and paclitaxel can stimulate tumor cells to produce IFN-b, serving as a signaling molecule that orchestrates the expression of MHC class I molecules which are critical for antigen presentation [40].”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [40]

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Cited by

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Authors
Wan, S., Pestka, S., Jubin, R. G., Lyu, Y. L., Tsai, Y.-C., & Liu, L. F.
Affiliations
University of Medicine and Dentistry of New Jersey (US)
Corresponding author
Liu, Leroy F.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-03-01
Volume
7
Issue
3
Pages
e32542
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0032542
PMC
PMC3291570
OpenAlex
W2118863472
Cited by
295
References
1
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FWCI
5.04
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Rutgers Cancer Institute of New Jersey
  • National Institutes of Health
  • National Cancer Institute (R01CA102463, R01CA039662, R01-CA39662)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
MHC class I expression, interferon-beta, type I interferon signaling, topotecan, breast cancer, antitumor immunity, IFNAR1, autocrine and paracrine signaling, tumor antigen presentation, metronomic chemotherapy, T cell cytotoxicity, topoisomerase I inhibitor, cytokines
MeSH terms
Antineoplastic Agents, Breast Neoplasms, Enzyme-Linked Immunosorbent Assay, Female, Genes, MHC Class I, Humans, Tumor Necrosis Factor-alpha, Histocompatibility Antigens Class I, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, Interleukin-8, NF-kappa B, Interferon-beta, Apoptosis, Topotecan, Cell Line, Tumor

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